Hyaluronic acid is a polysaccharide ether composed of alternate residues of D-glucuronic acid and N-acetyl-D.glycosamine. It is a straight-chained polymer with a molecular weight varying between 50,000 and 13,000,000 Da, depending on the source from which it is obtained and the methods of preparation and determination used. It is present in nature in pericellular gels, in the fundamental substance of the connective tissue of vertebrate organisms, of which it is one of the main components, in the synovial fluid of joints, in the vitreous humor, in human umbilical cord and in rooster combs.
Hyaluronic acid plays a vital role in many biological processes such as tissue hydration, proteoglycan organisation, cell differentiation, proliferation and angiogenesis (J. Aigner et al., L. Biomed. Mater. Res. 1998, 42, 172-181).
It is well known that fractions of hyaluronic acid can be used to facilitate tissue repair, as a substitute for the intraocular fluid, or administered by the intra-articular route to treat joint pathologies, as described in European patents Nos. 0138572 and 0535200.
Hyaluronic acid plays a fundamental role in the tissue repair process, especially in the first stages of granulation, stabilising the coagulation matrix and controlling its degradation, favouring the recruitment of inflammatory cells such as fibroblasts and endothelial cells and, lastly, orienting the subsequent migration of the epithelial cells.
It is known that the application of hyaluronic acid solutions can accelerate healing in patients affected by sores, wounds and burns. The role of hyaluronic acid in the various stages of the tissue repair process has been described by the construction of a theoretical model by P. H. Weigel et al.: “A model for the role of hyaluronic acid and fibrin in the early events during the inflammatory response and wound healing”, J. Theor. Biol., 119: 219, 1986.
The use of low-molecular-weight hyaluronic acid fractions to prepare pharmaceutical compositions with osteoinductive properties is also known (U.S. Pat. No. 5,646,129).
Hyaluronic acid derivatives maintain all the properties of the abovesaid glycosaminoglycan with the advantage of being processable in various forms and having adaptable solubility and degradation times according to the type and percentage of the derivation (EP 0216453B1).
Moreover, hyaluronic acid derivatives have new properties resulting from the insertion of specific molecules in the structure of the hyaluronic acid, For example, the sulphated derivatives of hyaluronic acid present anticoagulant properties and are resistant to hyaluronidase (WO 95/25751).
The total or partial esters of hyaluronic acid and its cross-linked derivatives are also known, as is their use in the pharmaceutical and cosmetic fields and in that of biodegradable materials (U.S. Pat. Nos. 4,851,521, 4,965,353 and 5,676,964). Patent application No. WO 93/20858 describes binding solutions and pastes containing hyaluronic acid and/or its ester derivatives used as bone fillers in surgery.
Lastly, hyaluronic acid esters have been processed in the form of non-woven fabrics according to the process described in the U.S. Pat. No. 5,520,916.
The hyaluronic acid derivatives in a three dimensional form and in particular the hyaluronic partial and total esters processed as non woven tissue have been used as supports for the preparation of biological materials containing cellullar components and/or products generated by said cellular components.
For example we can mention:                WO96/33750 describing an artificial human skin comprising:            a) a microperforated membrane based on a hyaluronic acid derivative on which keratinocytes are seeded and cultured,    b) an underlying non woven tissue based on a hyaluronic acid derivative wherein fibroblasts have been seeded and left to proliferate;            WO 97/18842 describing a biologic material comprising:            a) an efficient culture of autologous or homologous bone marrow stem cells partially or completely differentiated into specific connective tissue cells, further comprising the extracellular matrix secreted by said cells, or alternatively    a′) the extra cellular matrix secreted by completely or partially differentiate bone marrow stem cells or alternatively secreted by mature tissue cells.    b) a three dimensional matrix consisting of hyaluronic acid derivatives and in particular partial or total esters;            WO98/56897 dealing with a biological material comprising a three dimensional matrix of consisting of at least one derivative of hyaluronic acid on which endothelial, glandular cells are grown.        
All these biomaterials, whose main use, in the field of graft surgery, require complex and long cultivation steps, before the same be transplanted in the site wherein tissue regeneration is required. In addition said materials containing cellular components require expensive stockage procedure such as cryopreservation. The biological material like that disclosed in WO 97/18842 containing only the extracellular matrix, requires besides the cellular cultivation also the step of cellular components removal.
The need is felt to dispose of a biocompatible biomaterial not showing the aforementioned drawbacks.